The broad objectives of this research are to identify and characterize biochemical and physiologic changes in experimental animals exposed to industrial chemicals and other environmental contaminants. Emphasis is placed on obtaining information that will explain the biochemical basis of effects in intact animals and on identification of endogenous (e.g., adrenal hormones, glutathione) and exogenous (e.g., nutritional, drugs and chemicals) factors that modify these effects. Chemical agents of occupational health significance which are currently or will be investigated include: vinyl chloride, vinylidene chloride, 2- chlorobutadiene, trichloroethane, acrylamide, acrylonitrile and mercury compounds. The hepatotoxic action of vinylidene chloride in rats has been shown to be enhanced by fasting, depletion of liver glutathione, exposure to acetone. Toxic interactions between vinyl and vinylidene chloride were observed and the quality of the interaction appeared related to the temporal relationships of exposure to the two compounds. Acrylamide did not affect pyridine nucleotide cofactors formation and utilization in rat brain, and the possible effect of this compound on lipid metabolism in nerve tissue will be investigated. Depletion of kidney glutathione by various means resulted in a reduced uptake of methylmercury by kidneys of rats. Preliminary evidence suggests a possible role of amino acid carriers in the uptake of mercury by kidneys. These studies should provide basic information on mechanisms of toxic action of industrial chemicals and help to identify environmental and occupational variables that may alter susceptibility of workers to industrial chemicals. Inclusion of studies of dose-response relationships will be useful for developing health criteria as a basis of standard limits for exposure to the chemicals studied.